TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7951	24076;24077;24078	chr2:178719641;178719640;178719639	chr2:179584368;179584367;179584366
N2AB	7634	23125;23126;23127	chr2:178719641;178719640;178719639	chr2:179584368;179584367;179584366
N2A	6707	20344;20345;20346	chr2:178719641;178719640;178719639	chr2:179584368;179584367;179584366
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-64
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1546
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/T	None	None	0.001	N	0.3	0.133	0.247872288689	gnomAD-4.0.0	2.05267E-06	None	None	None	None	N	None	2.98811E-05	0	None	0	0	None	0	0	1.799E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.5405	ambiguous	0.5531	ambiguous	-1.818	Destabilizing	0.006	N	0.481	neutral	None	None	None	None	N
A/D	0.9167	likely_pathogenic	0.925	pathogenic	-3.119	Highly Destabilizing	0.497	N	0.74	deleterious	D	0.535355329	None	None	N
A/E	0.8756	likely_pathogenic	0.8827	pathogenic	-2.993	Highly Destabilizing	0.567	D	0.739	prob.delet.	None	None	None	None	N
A/F	0.8353	likely_pathogenic	0.8146	pathogenic	-0.902	Destabilizing	0.567	D	0.732	prob.delet.	None	None	None	None	N
A/G	0.2861	likely_benign	0.2936	benign	-1.511	Destabilizing	0.22	N	0.568	neutral	D	0.541849789	None	None	N
A/H	0.9373	likely_pathogenic	0.939	pathogenic	-1.739	Destabilizing	0.968	D	0.725	prob.delet.	None	None	None	None	N
A/I	0.3899	ambiguous	0.3835	ambiguous	-0.173	Destabilizing	0.06	N	0.675	neutral	None	None	None	None	N
A/K	0.9433	likely_pathogenic	0.949	pathogenic	-1.438	Destabilizing	0.567	D	0.738	prob.delet.	None	None	None	None	N
A/L	0.4133	ambiguous	0.392	ambiguous	-0.173	Destabilizing	0.157	N	0.565	neutral	None	None	None	None	N
A/M	0.4917	ambiguous	0.4646	ambiguous	-0.53	Destabilizing	0.832	D	0.719	prob.delet.	None	None	None	None	N
A/N	0.8152	likely_pathogenic	0.8198	pathogenic	-1.804	Destabilizing	0.567	D	0.753	deleterious	None	None	None	None	N
A/P	0.5235	ambiguous	0.5575	ambiguous	-0.456	Destabilizing	0.667	D	0.756	deleterious	N	0.515605233	None	None	N
A/Q	0.8726	likely_pathogenic	0.8766	pathogenic	-1.761	Destabilizing	0.726	D	0.727	prob.delet.	None	None	None	None	N
A/R	0.8893	likely_pathogenic	0.8964	pathogenic	-1.314	Destabilizing	0.567	D	0.755	deleterious	None	None	None	None	N
A/S	0.1611	likely_benign	0.1575	benign	-2.07	Highly Destabilizing	0.124	N	0.535	neutral	N	0.501589128	None	None	N
A/T	0.1215	likely_benign	0.1088	benign	-1.845	Destabilizing	0.001	N	0.3	neutral	N	0.489850272	None	None	N
A/V	0.1521	likely_benign	0.1539	benign	-0.456	Destabilizing	0.001	N	0.424	neutral	N	0.43783701	None	None	N
A/W	0.9701	likely_pathogenic	0.967	pathogenic	-1.585	Destabilizing	0.968	D	0.753	deleterious	None	None	None	None	N
A/Y	0.9328	likely_pathogenic	0.9293	pathogenic	-1.109	Destabilizing	0.726	D	0.744	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.